On uncovering and understanding interactions between bacteriophages and bacteria

Bacteriophages are viruses that infect bacteria and are the most common viral subdivision on Earth. They are extremely important for understanding microbial ecosystems, but nevertheless most phage species remain unstudied. For studied phages, often only genetic information is available, and their bacterial hosts are therefore unknown; information essential for viruses. These knowledge gaps are caused on the one hand by the fact that methods to identify bacterial hosts of phage species are labor-intensive, and on the other hand by the fact that methods to study whole phage populations hardly obtain information about host species. This thesis aimed to better understand phage-bacteria interactions and to use these interactions to uncover phages. First, we studied a protein domain characteristic of the bacterium-binding tail of crAss-like phages, which are widespread in human intestines. We describe how such protein domains evolve and identify several new phage species. This was followed by an extensive study of the molecular mechanisms in phages that can infect multiple bacterial species. Next, we report two methods of studying phages through their interactions with bacteria. In the first method, isolated bacterial cell walls are added to unknown phage mixtures. By analyzing the phages that bind to the cell walls, we identify their host and discover new phages at the same time. The second method allows us to isolate only the proteins with which phages interact from bacterial cell walls. We show that this method has the potential to analyze such interactions at the molecular level.